HMDH_GIBFU
ID HMDH_GIBFU Reviewed; 976 AA.
AC P0CT44; Q12577; Q12615;
DT 11-DEC-2013, integrated into UniProtKB/Swiss-Prot.
DT 11-DEC-2013, sequence version 1.
DT 03-AUG-2022, entry version 34.
DE RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase {ECO:0000303|PubMed:9000379};
DE Short=HMG-CoA reductasee {ECO:0000303|PubMed:9000379};
DE EC=1.1.1.34 {ECO:0000250|UniProtKB:Q4WHZ1};
GN Name=HMGR {ECO:0000303|PubMed:9000379}; Synonyms=HMGA;
OS Gibberella fujikuroi (Bakanae and foot rot disease fungus) (Fusarium
OS fujikuroi).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium;
OC Fusarium fujikuroi species complex.
OX NCBI_TaxID=5127;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=m567;
RX PubMed=9000379; DOI=10.1007/s002940050174;
RA Woitek S., Unkles S.E., Kinghorn J.R., Tudzynski B.;
RT "3-hydroxy-3-methylglutaryl-CoA reductase gene of Gibberella fujikuroi:
RT isolation and characterization.";
RL Curr. Genet. 31:38-47(1997).
CC -!- FUNCTION: HMG-CoA reductase; part of the first module of ergosterol
CC biosynthesis pathway that includes the early steps of the pathway,
CC conserved across all eukaryotes, and which results in the formation of
CC mevalonate from acetyl-coenzyme A (acetyl-CoA) (By similarity). In this
CC module, the cytosolic acetyl-CoA acetyltransferase catalyzes the
CC formation of acetoacetyl-CoA (By similarity). The
CC hydroxymethylglutaryl-CoA synthase then condenses acetyl-CoA with
CC acetoacetyl-CoA to form HMG-CoA (By similarity). The rate-limiting step
CC of the early module is the reduction to mevalonate by the 3-hydroxy-3-
CC methylglutaryl-coenzyme A (HMG-CoA) reductase HMGR (By similarity).
CC {ECO:0000250|UniProtKB:Q4WHZ1}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-mevalonate + CoA + 2 NADP(+) = (3S)-hydroxy-3-
CC methylglutaryl-CoA + 2 H(+) + 2 NADPH; Xref=Rhea:RHEA:15989,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:36464, ChEBI:CHEBI:43074,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.34;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10003};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
CC {ECO:0000250|UniProtKB:Q4WHZ1}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the HMG-CoA reductase family. {ECO:0000305}.
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DR EMBL; X94307; CAA63970.1; -; Genomic_DNA.
DR AlphaFoldDB; P0CT44; -.
DR SMR; P0CT44; -.
DR eggNOG; KOG2480; Eukaryota.
DR UniPathway; UPA00058; UER00103.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004420; F:hydroxymethylglutaryl-CoA reductase (NADPH) activity; IEA:UniProtKB-EC.
DR GO; GO:0015936; P:coenzyme A metabolic process; IEA:InterPro.
DR GO; GO:0008299; P:isoprenoid biosynthetic process; IEA:InterPro.
DR GO; GO:0016126; P:sterol biosynthetic process; IEA:UniProtKB-KW.
DR CDD; cd00643; HMG-CoA_reductase_classI; 1.
DR Gene3D; 1.10.3270.10; -; 1.
DR Gene3D; 3.30.70.420; -; 1.
DR Gene3D; 3.90.770.10; -; 1.
DR InterPro; IPR002202; HMG_CoA_Rdtase.
DR InterPro; IPR023074; HMG_CoA_Rdtase_cat_sf.
DR InterPro; IPR023076; HMG_CoA_Rdtase_CS.
DR InterPro; IPR004554; HMG_CoA_Rdtase_eu_arc.
DR InterPro; IPR023282; HMG_CoA_Rdtase_N.
DR InterPro; IPR009023; HMG_CoA_Rdtase_NAD(P)-bd_sf.
DR InterPro; IPR009029; HMG_CoA_Rdtase_sub-bd_dom_sf.
DR InterPro; IPR000731; SSD.
DR PANTHER; PTHR10572; PTHR10572; 1.
DR Pfam; PF00368; HMG-CoA_red; 1.
DR Pfam; PF12349; Sterol-sensing; 1.
DR PRINTS; PR00071; HMGCOARDTASE.
DR SUPFAM; SSF55035; SSF55035; 1.
DR SUPFAM; SSF56542; SSF56542; 1.
DR TIGRFAMs; TIGR00533; HMG_CoA_R_NADP; 1.
DR PROSITE; PS00066; HMG_COA_REDUCTASE_1; 1.
DR PROSITE; PS00318; HMG_COA_REDUCTASE_2; 1.
DR PROSITE; PS01192; HMG_COA_REDUCTASE_3; 1.
DR PROSITE; PS50065; HMG_COA_REDUCTASE_4; 1.
DR PROSITE; PS50156; SSD; 1.
PE 3: Inferred from homology;
KW Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism; Membrane;
KW NADP; Oxidoreductase; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..976
FT /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase"
FT /id="PRO_0000114452"
FT TOPO_DOM 1..36
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 37..57
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 58..64
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 65..85
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 86..90
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 91..111
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 112..169
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 170..190
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 191..193
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 194..214
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 215..272
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 273..293
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 294..401
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 402..422
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 423..976
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT DOMAIN 36..217
FT /note="SSD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT REGION 926..954
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 929..945
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 618
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 752
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 828
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 924
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10003"
FT BINDING 624..630
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 685..687
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 712..720
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 781..783
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 923..924
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 928..929
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P04035"
SQ SEQUENCE 976 AA; 105395 MW; 2B8F1C9F3CB5A714 CRC64;
MDHEGCQGQH PQQCCQWVSN AWSEFLDLLK NAETLDIVIM LLGYIAMHLT FVSLFLSMRK
MGSKFWLGIC TLFSSVFAFL FGLVVTTKLG VPISVILLSE GLPFLVVTIG FEKNIVLTRA
VMSHAIEHRR IQAQNSKSGK RSPDGSTQNM IQYAVQAAIK EKGFEIIRDY AIEIVILVIG
AASGVQGGLQ QFCFLAAWTL FFDFILLFTF YTAILSIKLR STVSSVMSIC VWPLRMMASR
RVAENVAKGD DELNRVRGDA PLFGRKSSSI PKFKVLMILG FIFVNIVNIC SIPFRNPSSM
STIRTWASSL GGVIAPLSVD PFKVASNGLD AILPTAKSNN RPTLVTVLTP IKYELEYPSI
HYALGSAASN PAYNDAFHHH FQGYGVGGRM VGGILKSLED PVLSKWIVIA LALSVALNGY
LFNVARWGIK DPNVPEHNID RNELARAREF NDTGSATLPL GEYVPPTPMR TQPSTPAITD
DEAEGLHMTK ARPANLPNRS NEELEKLLSE NALREMTDEE VISLSMRGKI PGYALEKTLG
DFTRAVKIRR SIIARNKAAA DITHSLDRSK LPYENYNWER FFGACCENVI GYMPLPVGVA
GPLVIDGQSY FIPMATTEGV LVASASRGCK AINSGGGAIT VLTADGMTRG PCVAFETLER
AGAAKLWLDS EAGQDMMKKA FNSTSRFARL QSMKTALAGT NLYIRFKTTT GDAMGMNMIS
KGVEHALSVM ANDGGFDDMQ IISVSGNYCT DKKAAALNWI DGRGKGVVAE AIIPGEVVRS
VLKSDVDSLV ELNVAKNLIG SAMAGSVGGF NAHAANIVAA IFLATGQDPA QVVESANCIT
IMKNLNGALQ ISVSMPSLEV GTLGGGTILE PQGAMLDILG VRGSHPTNPG DNARRLARII
GAAVLAGELS LCSALAAGHL VRAHMQHNRS AAPSRSTTPG SSHDARLTGH DQCPRALSVN
NVDERRRYSE VKAIDE
